Slight Activity Research Articles

The Expression of Cytokines and Chemokines Potentially Distinguishes Mild and Severe Psoriatic Non-Lesional and Resolved Skin from Healthy Skin and Indicates Different Stages of Inflammation

In the psoriatic non-lesional (PS-NL) skin, the tissue environment potentially influences the development and recurrence of lesions. Therefore, we aimed to investigate mechanisms involved in regulating tissue organization in PS-NL skin. Cytokine, chemokine, protease, and protease inhibitor levels were compared between PS-NL skin of patients with mild and severe symptoms and healthy skin. By comparing mild and severe PS-NL vs. healthy skin, differentially expressed cytokines and chemokines suggested alterations in hemostasis-related processes, while protease inhibitors showed no psoriasis severity-related changes. Comparing severe and mild PS-NL skin revealed disease severity-related changes in the expression of proteases, cytokines, and chemokines primarily involving methyl-CpG binding protein 2 (MECP2) and extracellular matrix organization-related mechanisms. Cytokine and chemokine expression in clinically resolved versus healthy skin showed slight interleukin activity, differing from patterns in mild and severe PS-NL skin. Immunofluorescence analysis revealed the severity-dependent nuclear expression pattern of MECP2 and decreased expression of 5-methylcytosine and 5-hydroxymethylcytosine in the PS-NL vs. healthy skin, and in resolved vs. healthy skin. Our results suggest distinct cytokine–chemokine signaling between the resolved and PS-NL skin of untreated patients with varying severities. These results highlight an altered inflammatory response, epigenetic regulation, and tissue organization in different types of PS-NL skin with possibly distinct, severity-dependent para-inflammatory states.

Immunohistochemical Expression of MDM2, Bcl-2, SATB2 and Ki-67 in Histological Variants of Unicystic Ameloblastoma.

To characterize the immunohistochemical expression of MDM2, Bcl-2, SATB2 and Ki-67 in histological variants of unicystic ameloblastoma (UA). Following the ethical approval, forty (40) patients with unicystic ameloblastoma were retrieved from the archives and subjected to immunohistochemistry (IHC). Sociodemographic and clinical data were also retrieved. The results were entered into a Microsoft Excel spreadsheet and analyzed using SPSS software. Human tooth germs, which served as the control, showed moderate expression of Bcl-2 and MDM2 with slight proliferative activity in ameloblasts and moderate expression of SATB2 in ectomesenchyme and odontoblasts. Luminal UA (Type 1) showed low Ki-67 index and negative to mild Bcl-2 and MDM2 expression, whilst Type 1.2 (luminal and intraluminal), Type 1.2.3 (luminal, intraluminal and mural), and Type 1.3 (luminal and mural), including the recurrent cases, showed moderate to intense expression with high mean Ki-67 index. The difference between the study groups was statistically significant (p value < 0.001). No expression of SATB2 was noted in any histological variant of UA. Furthermore, no significant differences were noted in age, gender, site and location between the groups. In contrast to luminal variant of UA, mural±intraluminal variants and recurrent cases demonstrate higher expression of Bcl-2 and MDM2 with higher mean Ki-67 index. It may thus be prudent to provide aggressive treatment for cases, not just with mural follicles but also for the patients with intraluminal plexiform proliferation, to prevent recurrence and improve patient outcomes.

The Antimicrobial Efficacy and Quality Changes in Pineapple Juice Treated with Natural Preservatives

The study investigated effects of natural preservatives on the quality of fresh pineapple fruit juice. The natural preservatives used are ginger, garlic, moringa seed and cloves and were processed into powder. The treatment of pineapple with the natural preservatives was at a concentration of 20% with 3 minutes dipping time. The enumeration and identification of microorganisms on the fresh pineapple fruit, shows that the total bacteria count was 1.8×105 colony forming unit per gram (CFU/g) and 4.6×103 CFU/g respectively. The identified bacteria are staphylococcus aureus and streptococcus spp and identified fungi were Aspergillus Niger, penicillin spp and Aspergillus perfrigens respectively. Moringa seed extract exhibited moderate antibacterial activity, with zones of inhibitions (ZOIs) of 16 mm against Staphylococcus aureus and 15 mm against Streptococcus spp. Garlic (GL) showed the least antibacterial activity among the natural preservative samples, with 9mm zones of inhibition against Staphylococcus aureus and 4 mm against Streptococcus spp. Clove extract displayed significant antibacterial activity, with 14 mm zones of inhibition against Staphylococcus aureus and 19 mm against Streptococcus spp. Ginger extract exhibited slight antibacterial activity, with zones of inhibition of 4 mm against both bacterial strains. Chemical composition of the treated pineapple juice result ranges from 0.77-0.865% TTA, 64.12-63.10 Vit C, 26.50-25.06 Brix Content,3.20-3.39 pH and 13.23-13.17 TSS respectively. The control (100% pineapple Juice) displayed balanced properties serving as an effective baseline3. Storage studies, ambient stored samples were analyzed at 0 day and 21 days intervals. All samples were subjected to standard analytical methods. Results showed increase in number of bacteria and fungi with increase in the number of days. The use of cloves, garlic, ginger, and moringa seeds as natural antimicrobial agents in pineapple juice is effective in controlling microbial growth, thus enhancing the safety and shelf life of the juice. These treatments also influence the chemical and sensory properties of the juice, contributing to consumer acceptability.

AGMATINE ADMINISTRATION ALLEVIATES NERVE DAMAGE AND IMPROVES NERVE FUNCTION IN METHOTREXATE INDUCED PERIPHERAL NEUROPATHY IN RATS

Objective: Chemotherapeutic agents can produce neurodegenerative changes. This study was conducted to assess the therapeutic potential of agmatine, a neuromodulator, on methotrexate induced neurodegeneration in sciatic nerve. Materials and Methods: 40 male Wistar albino rats were assigned into four groups at random as control, methotrexate, agmatine and methotrexate-agmatine. Methotrexate was injected intraperitoneally at a 37.5 mg/kg/week dose for 3 weeks. Afterwards, agmatine was administered intraperitoneally twice a day at a 40 mg/kg dose for 7 days. Sciatic functional index, nociceptive pain perception and behavioral changes were analyzed every week. Nerve conduction velocity was evaluated. Apoptotic activity and mitophagy, histopathological changes in sciatic nerves were examined. Results: Methotrexate administration resulted in a prolonged escape time to the platform and decreased the time spent in the quadrant in the water maze test; elevated nociceptive latencies; decreased the number of frames passed in the open field test; reduced sciatic NCV and SFI score. Besides, methotrexate administration caused a reduction in myelin thickness and axon diameter in sciatic nerve and a more intense glial fibrillary acidic protein immunoreactivity. Methotrexate administration triggered an increase in the Bax/Bcl-2 protein expression ratio without changing the expression level of Parkin, indicating a slight apoptotic activation. agmatine administration improved methotrexate induced changes in behavioral performances, nociceptive pain perception, nerve conduction, SFI scores and histopathological changes. Conclusion: Agmatine has been demonstrated to possess a therapeutic potential in methotrexate induced degeneration and peripheral neuropathy in the rat sciatic nerve.

Myrtus communis L. Essential Oil Exhibits Antiviral Activity against Coronaviruses.

Human coronaviruses are a continuous threat to the human population and have limited antiviral treatments, and the recent COVID-19 pandemic sparked interest in finding new antiviral strategies, such as natural products, to combat emerging coronaviruses. Rapid efforts in the scientific community to identify effective antiviral agents for coronaviruses remain a focus to minimize mortalities and global setbacks. In this study, an essential oil derived from Myrtus communis L. (MEO) is effective against HCoV-229E and HCoV-OC43 virus infections in comparison to two FDA-approved drugs, Remdesivir and Nirmatrelvir. Gas-chromatography and mass spectrometry were used to identify the chemical composition of MEO. Slight antioxidant activity was observed in MEO, indicating a role in oxidative stress. A dose-response curve measuring the EC50 indicates a high potency against HCoV-229E and HCoV-OC43 virus infections on Huh7.5 cells with low cytotoxicity using a PrestoBlue cell viability assay. Our findings demonstrate that MEO exhibits potent antiviral activity against HCoV-229E and HCoV-OC43 on Huh7.5 cells within a low-cytotoxicity range, but not on SARS-CoV-2. Artificial bacterial chromosome plasmids that expressed SARS-CoV-2 used for replicon-to determine viral replication and viral assembly/egress on HEK293T/17 cells-and virus-like particles on Huh7.5-AT cells-to determine viral entry and assembly/egress-showed no antiviral activity with MEO in comparison to Remdesivir. This study reveals the potential effectiveness of MEO as an alternative natural remedy to treat human coronaviruses and a potential antiviral agent for future coronavirus infections.

Effect of toxins from different periodontitis-associated bacteria on human platelet function.

Periodontitis is caused by a dysbiosis of oral bacteria resulting in alveolar bone destruction and teeth loss. The role of platelets in pathogenesis of periodontitis is a subject of research. The release of toxins from periodontitis-associated bacteria may influence platelet function and contribute to the modulation of hemostatic or inflammatory responses. Therefore, we explored platelet function upon exposure to defined toxins: leukotoxin A from Aggregatibacter actinomycetemcomitans (LtxA), a synthetic version of the C14-Tri-LAN-Gly peptide from Fusobacterium nucleatum (C14), and lipopolysaccharides from Porphyromonas gingivalis (LPS). Light transmission aggregometry was performed after the addition of toxins to platelet-rich plasma in different doses. Flow cytometry was used to identify inhibitory effects of toxins by measuring phosphorylation of the vaso-dilator-stimulated phosphoprotein or to identify activating effects by the detection of CD62P expression. The release of chemokines derived from washed platelets was determined by immunoassays. Collagen-induced threshold aggregation values were diminished upon incubation with LtxA and C14, accompanied with an increase of vaso-dilator-stimulated phosphoprotein (VASP) phosphorylation, indicating platelet inhibition. In contrast, LPS did not affect aggregation but slightly enhanced CD62P expression under co-stimulation with low-dose thrombin pointing to slight platelet activation. The three toxins did not relevantly influence the secretion of chemokines. Although weak, the investigated toxins differently influenced human platelet function. LtxA and C14 mediated inhibitory effects, whereas LPS contributed to a slight activation of platelets. Further analysis of specific cellular responses mediated by bacterial toxins may render novel targets and suggestions for the treatment of periodontitis.

Cellular Effects of Enterobacteriaceae Polysaccharide Colanic Acid.

Colanic acid (CA) is an exopolysaccharide found in Enterobacteriaceae. Recently, its ability to stimulate physical activity in mice and to prolong the lifespan of invertebrates has been described. In the current work, we use standard MTT assay, fluorescence microscopy, and flow cytometry to describe CA action on several cell lines of different origins. We observed slight antiproliferative activity against colorectal cancer (HCT-116), neuroblastoma (IMR-32), and myoblast (C2C12) cell lines at a concentration of 256 μg/mL, while other cell lines of non-cancerous origin (Vero, HPF) did not show any decrease in the MTT assay. In all cell lines, we observed a rearrangement of mitochondria localization using fluorescence microscopy. CA induces cell differentiation in the myoblast cell line (C2C12) at concentrations of 50-200 μg/mL. Briefly, we observed that the number of apoptotic cells increased and the metabolic activity in the MTT assay decreased, which was accompanied by changes in cell morphology, the quantity of ROS, and the potential of the mitochondrial membrane. Taken together, these results indicate that CA is specific in cytotoxicity to cell lines of different origins and can impact mitochondria and differentiation, consistent with its potential geroprotective function.

Pectin-based hydrogel loaded with polymeric nanocapsules for the cutaneous delivery of tacrolimus: A targeted approach for the treatment of psoriasis

This study aimed to develop a novel pectin-based hydrogel (PEC) incorporating nanocapsules-loaded tacrolimus (NCtac), named PEC-NCtac, as a potential strategy for psoriasis treatment. Blank nanocapsules (NC), PEC, PEC-NC, non-encapsulated tacrolimus (TAC), and the commercial TAC ointment (Tacroz®) were used as controls. The objectives involved physicochemical characterizing PEC-NCtac, assessing its cytotoxicity and anti-inflammatory effects, comparing adhesiveness with controls, determining skin penetration and permeation, and evaluating irritation potential. PEC-NCtac had an unimodal size distribution by laser diffraction (mean diameter of 250 nm and polydispersity -SPAN- of 1.68), drug content of 0.81 mg g−1 (HPLC), and pH of 4.51 (potentiometry). The nanoformulation had no significant impact on the viability of HaCat cells and CD4+ T cells when tested 24 h after treatment, with both cell types maintaining nearly 100 % viability. Treatment with NCtac resulted in a reduction in the pro-inflammatory cytokine IL-17A (p < 0.05). Adhesion studies revealed that PEC-NC showed a 1.9-fold higher force work compared to PEC. The combined effect of individual adhesion of NC and PEC when associated (PEC-NC) was evident in both healthy and injured skin (Healthy skin = 73 mN mm; Injured skin = 251 mN mm). PEC-NCtac allowed a decrease in skin drug permeation in the epidermis of injured skin compared to Tacroz® (40 % vs. 70 %, respectively). PEC-NCtac exhibited non-irritating activity in the HET-CAM/CAM-TBS model, while TAC demonstrated slight irritant activity. Furthermore, PEC-NCtac showed superior anti-inflammatory effects compared to TAC (75.0 % vs. 58 %, P value = 0.03). Summarizing, PEC-NCtac appears promising for topical treatment, demonstrating enhanced adhesion, skin penetration, safety profile, and anti-inflammatory activity.

Synthesis of new polyazomethine-based pyrazole moieties as promising biologically active macromolecules

ABSTRACT Using the polycondensation technique, it was possible to synthesize a new class of biologically active polyazomethine based on pyrazole moiety. The polymerization occurred through the interaction between terephthalaldehyde and various derivatives of diaminopyrazole. The polymers that were made were given the letters PAZm/Py1–4 to reflect the different diaminopyrazole derivatives that were used. The monomer and polymer structures were investigated by common spectral characterization methods. The new PAZm/Py1–4 were examined by gel permeation chromatography (GPC), solubility tests, thermogravimetric analysis (TGA), X-ray diffraction analysis (XRD), and scanning electron microscopy (SEM). The newly synthesized polymers have high thermal stability and normal crystalline behavior. The antibacterial properties of all synthesized polymers were evaluated against the Gram-positive bacteria and the Gram-negative bacteria. Additionally, two types of fungi were used to test how well the prepared polymers worked against fungi. PAZm/Py1 and PAZm/Py4 showed slight antibacterial activity against the representative Gram-positive bacteria, while PAZm/Py2 and PAZm/Py3 had no significant influence. All the tested polymers showed slight to moderate antibacterial activity against the representative Gram-negative bacteria. PAZm/Py1 and PAZm/Py4 had a greater antifungal influence than other polymers.

The Discovery of Novel α2a Adrenergic Receptor Agonists Only Coupling to Gαi/O Proteins by Virtual Screening.

Most α2-AR agonists derived from dexmedetomidine have few structural differences between them and have no selectivity for α2A/2B-AR or Gi/Gs, which can lead to side effects in drugs. To obtain novel and potent α2A-AR agonists, we performed virtual screening for human α2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity. Compound P300-2342 and its three analogs significantly decreased the locomotor activity of mice (p < 0.05). Furthermore, P300-2342 and its three analogs inhibited the binding of [3H] Rauwolscine with IC50 values of 7.72 ± 0.76 and 12.23 ± 0.11 μM, respectively, to α2A-AR and α2B-AR. In α2A-AR-HEK293 cells, P300-2342 decreased forskolin-stimulated cAMP production without increasing cAMP production, which indicated that P300-2342 activated α2A-AR with coupling to the Gαi/o pathway but without Gαs coupling. P300-2342 exhibited no agonist but slight antagonist activities in α2B-AR. Similar results were obtained for the analogs of P300-2342. The docking results showed that P300-2342 formed π-hydrogen bonds with Y394, V114 in α2A-AR, and V93 in α2B-AR. Three analogs of P300-2342 formed several π-hydrogen bonds with V114, Y196, F390 in α2A-AR, and V93 in α2B-AR. We believe that these molecules can serve as leads for the further optimization of α2A-AR agonists with potentially few side effects.

Detergent-resistant α-amylase derived from Anoxybacillus karvacharensis K1 and its production based on whey

In the field of biotechnology, the utilization of agro-industrial waste for generating high-value products, such as microbial biomass and enzymes, holds significant importance. This study aimed to produce recombinant α-amylase from Anoxybacillus karvacharensis strain K1, utilizing whey as an useful growth medium. The purified hexahistidine-tagged α-amylase exhibited remarkable homogeneity, boasting a specific activity of 1069.2 U mg−1. The enzyme displayed its peak activity at 55 °C and pH 6.5, retaining approximately 70% of its activity even after 3 h of incubation at 55 °C. Its molecular weight, as determined via SDS-PAGE, was approximately 69 kDa. The α-amylase demonstrated high activity against wheat starch (1648.8 ± 16.8 U mg−1) while exhibiting comparatively lower activity towards cyclodextrins and amylose (≤ 200.2 ± 16.2 U mg−1). It exhibited exceptional tolerance to salt, withstanding concentrations of up to 2.5 M. Interestingly, metal ions and detergents such as sodium dodecyl sulfate (SDS), Triton 100, Triton 40, and Tween 80, 5,5ʹ-dithio-bis-[2-nitrobenzoic acid (DNTB), β-mercaptoethanol (ME), and dithiothreitol (DTT) had no significant inhibitory effect on the enzyme’s activity, and the presence of CaCl2 (2 mM) even led to a slight activation of the recombinant enzyme (1.4 times). The Michaelis constant (Km) and maximum reaction rate (Vmax), were determined using soluble starch as a substrate, yielding values of 1.2 ± 0.19 mg mL−1 and 1580.3 ± 183.7 μmol mg−1 protein min−1, respectively. Notably, the most favorable conditions for biomass and recombinant α-amylase production were achieved through the treatment of acid whey with β-glucosidase for 24 h.

Antiviral properties of titanium nanoparticles and features of their influence on the morphology of virions

The search for new antiviral substances and the development of modern antiviral preparations and disinfectants is an important area of modern science. Nanoparticles (NPs) and nanomaterials (NMs) have received increasing attention from scientists as promising antiviral substances recently. Our study aimed to investigate the antiviral activity of citrate-stabilized titanium nanoparticles (Ti NPs) against Teschovirus A (TV-A) and Potato virus Y (PVY). The biological activity of PVY has been tested using cultivated tobacco plants (Nicotiana tabacum L.) and bell pepper plants (Capsicum annum L.). It has been found that injection of plants with the virus has led to the appearance of PVY infection symptoms with further death of the plants. The threshold limit value (TLV) for Ti NPs in embryonic pig kidney cell line culture is 12.5 µg/cm3. According to the prophylactic and treatment plots, Ti NPs have slight antiviral activity against TV-A strain Dniprovskyi 34, decreasing its titer according to both plots by 0.5 lg TCD50/cm3. However, according to the virucidal plot at TLV concentration, Ti NPs show high antiviral activity against TV-A strain Dniprovskyi 34, significantly decreasing its titer in embryonic pig kidney cell line culture by 4.46 lg TCD50/cm3. Ti NPs do not have antiviral activity against PVY, according to the prophylactic and treatment plots. Nevertheless, according to the virucidal plot Ti NPs showed high antiviral activity against PVY, inactivating the virus in the reaction mixture in vitro. According to the results of TEM, Ti NPs bind to virus particles. Virus particles with NPs attached to them, deformed and partially destroyed virus particles have been found in samples of virus-containing suspension, which were incubated with Ti NPs. We suggest that Ti NPs are useful as disinfectants to control viral infections, particularly TV-A and PVY.

Co-Immobilization of ADH and GDH on Metal-Organic-Framework: An Effective Biocatalyst for Asymmetric Reduction of Ketones.

Chiral alcohols are not only important building blocks of various bioactive natural compounds and pharmaceuticals, but can serve as synthetic precursors for other valuable organic chemicals, thus the synthesis of these products is of great importance. Bio-catalysis represents one effective way to obtain these molecules, however, the weak stability and high cost of enzymes often hinder its broad application. In this work, we designed a biological nanoreactor by embedding alcohol dehydrogenase (ADH) and glucose dehydrogenase (GDH) in metal-organic-framework ZIF-8. The biocatalyst ADH&GDH@ZIF-8 could be applied to the asymmetric reduction of a series of ketones to give chiral alcohols in high yields (up to 99 %) and with excellent enantioselectivities (>99 %). In addition, the heterogeneous biocatalyst could be recycled and reused at least four times with slight activity decline. Moreover, E. coli containing ADH and GDH was immobilized by ZIF-8 to form biocatalyst E. coli@ZIF-8, which also exhibits good catalytic behaviours. Finally, the chiral alcohols are further converted to marketed drugs (R)-Fendiline, (S)-Rivastigmine and NPS R-568 respectively.

Pro-inflammatory properties of aureocin A53

Aureocin A53 is a peptide bacteriocin produced by an opportunistic pathogen Staphylococcus aureus strain A53. The spatial structure of aureocin, unlike its amino acid sequence, is similar to the bacteriocin BacSp222, which was recently found to have the ability to induce the inflammatory response in the host cells. The presented research aimed to verify such properties also for aureocin A53. We demonstrated that the synthetic aureocin has slight cytotoxic activity towards murine monocytic-macrophage cells. This molecule was also able to activate murine P388.D1 and RAW 264.7 cells to IFN-γ-dependent production of nitric oxide and to activate production of the pro-inflammatory cytokine - TNF. We also proved that the observed pro-inflammatory activity of the studied bacteriocin is related to the stimulation of the TLR2/TLR6 heterodimer and, consequently, activation of the NF-κB transcription factor. To sum up, A53 is the second bacteriocin described in the literature, showing the pro-inflammatory activity against murine macrophage-like cells.

Does the Invasive Heracleum mantegazzianum Influence Other Species by Allelopathy?

Heracleum mantegazzianum is an invasive species in middle Europe. The mode of action of its invasiveness is still not known. Our study focuses on observation of potential allelopathic influence by the production and release of phytochemicals into its environment. Plant material was collected four times within one season (April, May, June, July 2019) at locality Lekárovce (eastern Slovakia) for comparison of differences in composition and potential allelopathy. Water extracts from collected samples were used for different biological assays. The total phenols and flavonoids were determined spectrophotometrically. The profile and content of phenolic components, including coumarins, were determined by two techniques of liquid chromatography along with in vitro evaluation of the free radical scavenging activity of extracts (DPPH, Hydroxyl, Superoxide, and FRAP). The changes in composition in extracts in different seasonal periods were evident as well as potential phytotoxic activity in some concentrations on specific model plants. The slight antioxidant activity was noted. The invasiveness of the current species could be supported by the excretion of its phytochemicals into its surroundings and by different modes of action influencing living organisms in its environment.

Adaptogenic correction of free radical processes in liver tissue under the exposure to coal-rock dust on the body (experimental study)

Introduction. Damage to the liver under the conditions of long-term exposure to coal-rock dust on the body leads to significant impairment of its metabolic, detoxification, synthetic, and other functions. In this regard, it is relevant to search for early methods of prevention and correction of developing pathological changes in this organ. The purpose of the study is to experimentally study the effect of a complex drug with dihydroquercetin on the activity of free radical processes in the liver of laboratory rats over the dynamics of long-term exposure to coal-rock dust. Materials and methods. The work was carried out on male white rats weighing 200–250 g. The control group was kept under the standard vivarium conditions. The experimental group included rats that inhaled coal-rock dust in a priming chamber daily for 4 hours for 1, 3, 6, and 9 weeks and rats that received a daily complex drug with dihydroquercetin immediately before dust exposure. In the liver tissue, the activity of free radical oxidation and antioxidant defense enzymes (superoxide dismutase and catalase) was determined. Results. Priming rats with coal-rock dust for three weeks led to the gain in the intensity of free radical processes in the liver tissue: the initial level of accumulation of TBA-active oxidation products reliably raised by almost 2 times over the 1st week and 3 times over the 3rd week of the experiment compared to the control. An increase in the intensity of free radical oxidation was accompanied by activation of antioxidant defense enzymes - catalase - by 2.4 times at the 1st week and 1.6 times at the 3rd week of dust exposure. Raising the period of priming with dust up to 9 weeks led to multidirectional changes in oxidative metabolism in the liver tissue: at week 6, a decrease in the activity of superoxide dismutase was almost 3 times; at week 9, to a slight activation of antioxidant enzymes: superoxide dismutase by 55% and catalase by 36%.The most effective use of a complex drug with dihydroquercetin had been shown in short-term mode for three weeks, but not long-term (more than 6 weeks). The maximum antioxidant defense effect of dihydroquercetin was detected at the 3rd week of dust exposure – the level of free radical products decreased by 2 times and the activity of superoxide dismutase increased by 4 times. Limitations. Since the issue of organ-specific effects and the optimal duration of use of dihydroquercetin to increase resistance to free radical damage has been little elaborated, this imposes certain restrictions on its use for the correction and prevention of occupational diseases. Conclusion. The results obtained should be taken into account with long-term use of exogenous antioxidants in the correction and prevention of occupational diseases to support the level of endogenous antioxidant systems in the cell and the protective effect of dihydroquercetin for tissues most sensitive to the action of free radical processes.

Corrected and republished from: "Vibrio fischeri Possesses Xds and Dns Nucleases That Differentially Influence Phosphate Scavenging, Aggregation, Competence, and Symbiotic Colonization of Squid".

Cells of Vibrio fischeri colonize the light organ of Euprymna scolopes, providing the squid bioluminescence in exchange for nutrients and protection. The bacteria encounter DNA-rich mucus throughout their transition to a symbiotic lifestyle, leading us to hypothesize a role for nuclease activity in the colonization process. In support of this, we detected abundant extracellular nuclease activity in growing cells of V. fischeri. To discover the gene(s) responsible for this activity, we screened a V. fischeri transposon mutant library for nuclease-deficient strains. Interestingly, only one strain, whose transposon insertion mapped to nuclease gene VF_1451, showed a complete loss of nuclease activity in our screens. A database search revealed that VF_1451 is homologous to the nuclease-encoding gene xds in Vibrio cholerae. However, V. fischeri strains lacking xds eventually revealed slight nuclease activity on plates upon prolonged incubation. This led us to hypothesize that a second secreted nuclease, identified through a database search as VF_0437, a homolog of V. cholerae dns, might be responsible for the residual nuclease activity. Here, we show that Xds and/or Dns are involved in essential aspects of V. fischeri biology, including natural transformation, aggregation, and phosphate scavenging. Furthermore, strains lacking either nuclease were outcompeted by the wild type for squid colonization. Understanding the specific role of nuclease activity in the squid colonization process represents an intriguing area of future research.IMPORTANCEFrom soil and water to host-associated secretions such as mucus, environments that bacteria inhabit are awash in DNA. Extracellular DNA (eDNA) is a nutritious resource that microbes dedicate significant energy to exploit. Calcium binds eDNA to promote cell-cell aggregation and horizontal gene transfer. eDNA hydrolysis impacts the construction of and dispersal from biofilms. Strategies in which pathogens use nucleases to avoid phagocytosis or disseminate by degrading host secretions are well-documented; significantly less is known about nucleases in mutualistic associations. This study describes the role of nucleases in the mutualism between Vibrio fischeri and its squid host Euprymna scolopes. We find that nuclease activity is an important determinant of colonization in V. fischeri, broadening our understanding of how microbes establish and maintain beneficial associations.

Inner speech and the body error theory.

Inner speech is commonly understood as the conscious experience of a voice within the mind. One recurrent theme in the scientific literature is that the phenomenon involves a representation of overt speech, for example, a representation of phonetic properties that result from a copy of speech instructions that were ultimately suppressed. I propose a larger picture that involves some embodied objects and their misperception. I call it "the Body Error Theory," or BET for short. BET is a form of illusionism, but the particular version I favor is a cross-modal illusion. Newly described here, my hypothesis is that the experience of inner speech arises from a mix of interoception and audition. Specifically, there is the detection of slight but well-confirmed activities in the speech musculature that occur during inner speech, which helps to transform representations of normal but quiet nonverbal sounds that inevitably occur during inner speech, from breathing to background noise, into a mistaken perception of inner speech. Simply put, activities in the speech musculature mix with sounds to create the appearance of speech sounds, which thus explains the "voice within the mind." I also show how BET's cross-modal system fits with standard information processing accounts for speech monitoring and how it accommodates the central insights of leading theories of inner speech. In addition, I show how BET is supported by data from experience-sampling surveys and how it can be empirically tested against its rivals.

Cynara cardunculus L. var. scolymus L. Landrace "Carciofo Ortano" as a Source of Bioactive Compounds.

The preservation of agricultural biodiversity and socioeconomic development are relevant both to enhance domestic production and to support innovation. In the search for new biomolecules, we have focused on the "Carciofo Ortano" landrace, growth in the northern part of the Lazio region. Artichoke cultivation generates substantial by-products, including leaves, stems, and roots, which could serve as valuable sources of biomolecules and prebiotic dietary fiber. To valorize the leaf waste of the "Carciofo Ortano" landrace, a multidisciplinary approach was applied. Chemical analysis using HPLC-DAD identified mono-O- and di-O-caffeoylquinic acids and the sesquiterpene cynaropicrin in all artichoke leaf extracts. SPME-GC/MS analyses detected aliphatic alcohols in the fresh leaf samples. Antiproliferative and cytotoxic studies on cancer (SH-SY5Y, MCF-7, MDA) and normal (MCF-10A) human cell lines revealed that leaf extracts induced a selective dose and time-dependent biological effect. While showing slight activity against environmental bacterial strains, artichoke leaf extracts exhibited significant antifungal activity against the phytopathogenic fungus Alternaria alternata. Overall, the results highlight the potential of "Carciofo Ortano" cultivation by-products as a rich source of biomolecules with versatile applications in humans, animals, and the environment.

Improved mucoadhesivity of polyelectrolyte complexes films by electrospinning for the release of nystatin in the oral cavity

This work aimed to obtain and characterize chitosan-gum arabic polyelectrolyte complex films loaded with nystatin employing the “Solvent-Casting” technique. These films were covered with electrospun nanofibers of polycaprolactone-polycarbophil (Noveon® AA-1) to improve the mucoadhesivity of the system with the objective of increasing the residence time in the oral zone and act as sustained release systems of the drug. The topography of the films was determined by SEM, while the interaction of the polymers was evaluated by FTIR, DSC and TGA. The antimicrobial activity of the film was tested against a strain of Candida species, and the mucoadhesión capacity was determined in an in vitro model. The films are mucoadhesive and generate sustained release that can be explained by the Korsemeyer-Peppas model. Furthermore, significant antimicrobial activity was found. The films and their components showed a non-toxic to slight cytotoxic activity. These results indicate that these films based on polyelectrolyte complexes, potentiated by electrospun fibers are a plausible system for the controlled release of nystatin in the oral cavity.